Microbe of the Month: A few drops of poison had her talking again: The toxin that causes botulism also has beneficial uses, says Bernard Dixon

IT BEGAN as a respiratory infection, which left the 32-year-old travel agent somewhat hoarse. Then, as the months went by, she found that she could not control her voice properly. There were strange and frequent changes in pitch, and breaks in delivery.

The woman was offered speech therapy but without any lasting benefit. Next she tried psychological counselling, as her doctor suspected that the mysterious speech disorder could have resulted from the stresses of her job and recent divorce. This too failed to bring relief from the distressing affliction, which worsened over the next two years.

Although the condition then began to stabilise, it did not abate. During the following three years, the patient experimented with a wide range of possible remedies, from hypnosis and acupuncture to tranquillisers and other drugs. But nothing seemed to work, and she was forced to take up a new job in which she was not required to speak. Gradually, she reduced her social contacts, became chronically depressed and was given long-term medication.

At this point, the woman's psychiatrist referred her to the National Institutes of Health in Bethesda, Maryland. There, a laryngologist used a fibre optic endoscope to peer into the patient's throat, and discovered that some of the muscles responsible for speech were having uncontrollable spasms. Although they looked perfectly normal, the vocal cords showed spasmodic contractions that were causing the weird gaps and changes in pitch in the woman's voice.

It was this discovery that immediately suggested a potential panacea - botulinum A toxin, one of the most poisonous substances known. Injected in tiny quantities into the appropriate muscles, it relieved the woman's symptoms and greatly reduced the effort she required to speak. Her voice was no longer interrupted, and examination of her vocal cords showed that they were behaving normally.

Although the condition began to recur three months later, it stabilised without becoming as severe as before, and responded to further injections of toxin. Subsequent treatment was required but with decreasing doses at increasing intervals of time, and the woman was able to return to work as a travel agent and rebuild her social life.

Bizarre though the story may appear, it represents just one of many successes over the past decade in using an otherwise extremely dangerous microbial product for therapeuti cpurposes.

Made by the bacterium Clostridium botulinum, botulinum A toxin is responsible for botulism, a rare and often fatal form of food poisoning. It works by stopping nerve endings releasing acetylcholine, a chemical that communicates with other nerve endings. This weakens the muscles controlled by those nerves, preventing them from contracting.

The initial consequences, in untreated botulism, are blurred or double vision, followed by increasing difficulty in swallowing and breathing.

Dr Alan Scott, working at the Smith Kettlewell Eye Research Foundation in San Francisco, was the first to realise that this potentially fatal action might be exploited to beneficial effect, first of all in the treatment of squint. He reasoned that a minute dose of botulinum A toxin would relax the over-reacting muscles responsible for the abnormal position of the eye. It worked. Patients were helped, the principle was vindicated, and this approach to squint is now firmly established, sometimes combined with surgery.

However, since first being used in the UK in 1983, botulinum A toxin has turned out to be even more useful for other conditions characterised by dystonia (ie, uncontrollable muscle spasms). They include focal dystonias, which affect a limb or other part of the body, and spasmodic torticollis, which paralyses the neck muscles, causing the patient's head to twist to one side, forwards or backwards.

One of the most distressing dystonias is blepharospasm. Sufferers blink uncontrollably and may be unable to prevent their eyes from remaining permanently closed. There are more than 4,000 known cases of blepharospasm in the UK and at least 20,000 victims of all types of dystonia.

Botulinum A toxin, now marketed by Porton Products Ltd, of Porton Down, Wiltshire, has already helped thousands of individuals incapacitated by muscle spasms that were hitherto untreatable, often painful, and devastating in terms of employment, leisure activities and social life. For example, it relieves the symptoms totally in almost a third of patients with blepharospasm.

Similarly encouraging results have been reported in conditions ranging from writer's cramp and musicians' dystonias to golfer's 'yips' and dart player's cramp. Very recently, work at the Columbia-Presbyterian Medical Center, New York, indicated that the toxin can be used to improve

the speech of some people who stutter.

For the moment, botulinum A toxin is relatively expensive (about pounds 100 per injection for blepharospasm). Injections sometimes need to be repeated three or four times a year. And it is possible that patients may develop antibodies that reduce the effectiveness of the treatment.

Nevertheless, the advances of the past decade, the continuing extension of the range of conditions amenable to this approach and current research on other types of botulinum toxin indicate that Clostridium botulinum will play a major role in the future of human medicine.